Anthrax pathophysiology: Difference between revisions

Jump to navigation Jump to search
m (Bot: Removing from Primary care)
 
(248 intermediate revisions by 7 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Anthrax}}
{{Anthrax}}
{{CMG}}
{{CMG}}; {{AE}} {{JS}}
==Overview==  
==Overview==  
{{Main|Bacillus anthracis}}
The [[genetic]] material of [[Bacillus anthracis]] is coded within 1 [[chromosome]] and 2 [[plasmids]], which are fundamental for its [[toxicity]]. The [[spores]] of [[B. anthracis]] are the [[infectious]] form and can remain dormant in the environment for decades. The disease may be transmitted through the [[skin]], [[gastrointestinal]] or [[respiratory]] systems. The [[bacterium]] causes disease through 2 mechanisms: [[toxemia]] and [[bacterial infection]].<ref name="LiuMoayeri2014">{{cite journal|last1=Liu|first1=Shihui|last2=Moayeri|first2=Mahtab|last3=Leppla|first3=Stephen H.|title=Anthrax lethal and edema toxins in anthrax pathogenesis|journal=Trends in Microbiology|volume=22|issue=6|year=2014|pages=317–325|issn=0966842X|doi=10.1016/j.tim.2014.02.012}}</ref>  [[B. anthracis]] begins to produce [[toxins]] within hours of germination.<ref name="HannaIreland1999">{{cite journal|last1=Hanna|first1=Philip C.|last2=Ireland|first2=John A.W.|title=Understanding Bacillus anthracis pathogenesis|journal=Trends in Microbiology|volume=7|issue=5|year=1999|pages=180–182|issn=0966842X|doi=10.1016/S0966-842X(99)01507-3}}</ref>  Protective antigen (PA) and edema factor (EF) combine to form edema toxin (ET), and PA and lethal factor (LF) combine to form lethal toxin (LT), the active [[toxins]]. [[Bacterial]] [[toxins]] have a direct [[cytotoxic]] effect by interfering with [[cellular]] pathways, being also responsible for weakening the [[immune system]], so the initial systemic [[infection]] may occur. Anthrax lesions at any site are characterized by [[lymphadenopathy]], extensive [[edema]], [[necrosis]] and confluent [[exudate]] containing [[macrophages]] and [[neutrophils]]. If not stopped, the [[infection]] may affect different [[organs]], causing [[septicemia]] and potentially death.
[[Image:Anthrax - inhalational.jpg|thumb|left|250px|Inhalational anthrax - [[mediastinum|Mediastinal]] widening]]
''Bacillus anthracis'' is a rod-shaped [[Gram-positive]] bacterium, about 1 by 9 micrometers in size. It was shown to cause disease by [[Robert Koch]] in 1877. [http://german.about.com/library/blerf_koch.htm] The bacterium normally rests in [[endospore]] form in the soil, and can survive for decades in this state. Once ingested by a ruminant or placed in an open cut, the bacterium begins multiplying inside the animal or human  and in a few days to a month  kills it. Veterinarians can often tell  a possible  anthrax induced death by its sudden occurrence and by the blood and bloody fluids that oozed from the body orifices. Most anthrax bacteria inside the body are destroyed by anaerobic bacteria that can grow without oxygen. The greater danger lies in the bodily fluids and blood that spills from the body and spill into the soil where the anthrax bacteria turn into a dormant protective spore form. Once formed the spores are very hard to eradicate.


The infection of ruminants (and occasionally humans) normally proceeds as follows: once the spores are inhaled they are transported through the air passages into the tiny air sacs (alveoli) in the lungs. The spores are then picked up by scavenger cells (macrophages) in the lungs and are transported through small vessels (lymphatics) to the glands (lymph nodes) in the central chest cavity (mediastinum). Damage caused by the anthrax spores and bacilli to the central chest cavity  lungs can cause chest pain and difficulty breathing.   Once in the lymph  glands, the spores germinate into active  bacillus, that  multiplies, and eventually bursts the macrophage cell, releasing many more bacilli into the bloodstream which are transferred to the entire body. Once in the blood stream these bacilli release a tripartite toxin (composed of lethal factor, edema factor and protective antigen) which is known to be the primary agents of tissue destruction, bleeding, and death. If antibiotics are given too late, even if the antibiotics eradicate the bacteria, some people still will die because the toxins produced by the bacilli still remain in their system at lethal dose levels.
==Genetics==
The [[genetic]] component of [[Bacillus anthracis]] includes 1 [[chromosome]] and 2 [[plasmids]]. These [[plasmids]] (pXO1 and pXO2) are fundamental for its [[toxicity]]:<ref name="LiuMoayeri2014">{{cite journal|last1=Liu|first1=Shihui|last2=Moayeri|first2=Mahtab|last3=Leppla|first3=Stephen H.|title=Anthrax lethal and edema toxins in anthrax pathogenesis|journal=Trends in Microbiology|volume=22|issue=6|year=2014|pages=317–325|issn=0966842X|doi=10.1016/j.tim.2014.02.012}}</ref>


In order to enter the cells, the toxins use another protein produced by ''B. anthracis'', protective antigen. Edema factor inactivates [[neutrophil]]s (a type of phagocytic cell) so that they cannot phagocytose bacteria.  Historically, it was believed that lethal factor caused macrophages to make [[TNF-alpha]] and [[IL1B|interleukin 1, beta]] (IL1B), both normal components of the immune system used to induce an inflammatory reaction, ultimately leading to [[septic shock]] and death. However, recent evidence indicates that anthrax also targets endothelial cells (cells that lines serous cavities, lymph vessels, and blood vessels), causing vascular leakage (similar to hemorrhagic bleeding), and ultimately [[hypovolemic shock]] (low blood volume), and not only septic shock. In other words the patient bleeds to death internally.
* pXO1 - encodes 3 components of the anthrax [[exotoxin]]s:
:* Protective Antigen (PA)
:* Lethal Factor (LF)
:* Edema Factor (EF)


The virulence of a strain of anthrax is dependent on multiple factors, primarily the poly-D-glutamic acid capsule that protects the bacterium from phagocytosis by host neutrophils and its [[anthrax toxin|toxins]], edema toxin and lethal toxin.
* pXO2 - encodes proteins involved in the [[glutamic acid]] [[capsule]] structure which is responsible for conferring [[resistance]] against [[phagocytosis]].
==Pathophysiology==
=== Exposure ===
Occupational exposure to infected animals or their products (such as skin wool and meat) is the usual pathway of exposure for humans. Workers who are exposed to dead animals and animal products are at the highest risk, especially in countries where anthrax is more common.  Anthrax in livestock  grazing on open range where they mix with wild animals still occasionally occurs in the [[United States]] and elsewhere.  Many workers who deal  with wool and animal hides are routinely exposed to low  levels of anthrax spores but most exposures are not sufficient  to develop anthrax infections. Presumably, the body’s natural defenses can destroy low levels of exposure. These people usually contract cutaneous anthrax if they catch anything. Historically, the most dangerous form of inhalation anthrax was called [[Anthrax#Pulmonary (pneumonic, respiratory, or inhalation) anthrax|Woolsorters' disease]] because it was an occupational hazard for people who sorted wool. Fortunately this is now a very rare form of infection because of the much reduced incidence of anthrax disease in animals.
The last fatal case of natural inhalation anthrax in the United States occurred in California in 1976, when a home weaver died after working with infected wool imported from Pakistan. The autopsy was done at UCLA hospital. To minimize the chance of spreading the disease, the deceased was transported to UCLA in a sealed plastic body bag within a sealed metal container. The details of this case have been described in a medical journal '''Human Pathology''' (Volume 9, pages 594-597, September, 1978).


In July 2006 an artist who worked with untreated animal skins became the first person in more than 30 years to die in the United Kingdom from anthrax.<ref>[http://news.independent.co.uk/uk/health_medical/article1219711.ece Artist dies from anthrax caught from animal skins] Independent News and Media Limited, [[17 August]] 2006. Retrieved [[6 October]] 2006. </ref>
==Transmission==
The route of transmission of anthrax allows for its classification into the following:<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>
* Cutaneous anthrax - commonly requires a prior [[skin lesion]] as a prerequisite for [[infection]]
* Gastrointestinal anthrax - contracted following [[ingestion]] of contaminated food, primarily meat from an animal that died of the disease, or conceivably from [[ingestion]] of contaminated water
* Inhalational anthrax - from breathing in airborne anthrax [[spores]]  
* Injection anthrax - from the injection of a [[drug]] containing or contaminated with [[Bacillus anthracis]]


=== Mode of infection ===
==Pathogenesis==
Anthrax can enter the human body through the intestines ('''ingestion'''), lungs ('''inhalation'''), or skin ('''cutaneous''') and causes distinct clinical symptoms based on its site of entry. An infected human will generally be quarantined. However, anthrax does not usually spread from an infected human to a noninfected human. But if the disease is fatal the person’s body and its mass of anthrax bacilli becomes a potential source of infection to others and special precautions should be used to prevent more contamination. Unfortunately inhalation anthrax, if left untreated until obvious symptoms occur, will usually result in death if treatment is started too late.
[[B. anthracis]], the causative agent of anthrax, is a [[spore]]-forming [[bacterium]]. The [[spores]] of [[B. anthracis]], which can remain dormant in the environment for decades, are the [[infectious]] form, but this vegetative form of [[B. anthracis]] rarely causes disease.<ref name="ShadomySmith2008">{{cite journal|last1=Shadomy|first1=Sean V.|last2=Smith|first2=Theresa L.|title=Anthrax|journal=Journal of the American Veterinary Medical Association|volume=233|issue=1|year=2008|pages=63–72|issn=0003-1488|doi=10.2460/javma.233.1.63}}</ref> The [[bacterium]] causes disease through 2 mechanisms: [[toxemia]] and [[bacterial infection]].<ref name="LiuMoayeri2014">{{cite journal|last1=Liu|first1=Shihui|last2=Moayeri|first2=Mahtab|last3=Leppla|first3=Stephen H.|title=Anthrax lethal and edema toxins in anthrax pathogenesis|journal=Trends in Microbiology|volume=22|issue=6|year=2014|pages=317–325|issn=0966842X|doi=10.1016/j.tim.2014.02.012}}</ref>
[[Spores]] introduced through the [[skin]] lead to [[cutaneous]] or injection anthrax; those introduced through the [[gastrointestinal]] tract lead to gastrointestinal anthrax; and those introduced through the [[lungs]] lead to inhalation anthrax. After entering a human or animal, [[B. anthracis]] [[spores]] are believed to germinate locally or be [[phagocytosed]] by [[dendritic cells]] and [[macrophages]]. These will then carry the [[spores]] to the [[lymph nodes]], where they germinate.<ref name="Ross1957">{{cite journal|last1=Ross|first1=Joan M.|title=The pathogenesis of anthrax following the administration of spores by the respiratory route|journal=The Journal of Pathology and Bacteriology|volume=73|issue=2|year=1957|pages=485–494|issn=0368-3494|doi=10.1002/path.1700730219}}</ref><ref name="LiuMoayeri2014">{{cite journal|last1=Liu|first1=Shihui|last2=Moayeri|first2=Mahtab|last3=Leppla|first3=Stephen H.|title=Anthrax lethal and edema toxins in anthrax pathogenesis|journal=Trends in Microbiology|volume=22|issue=6|year=2014|pages=317–325|issn=0966842X|doi=10.1016/j.tim.2014.02.012}}</ref>
[[B. anthracis]] begins to produce [[toxins]] within hours of germination.<ref name="HannaIreland1999">{{cite journal|last1=Hanna|first1=Philip C.|last2=Ireland|first2=John A.W.|title=Understanding Bacillus anthracis pathogenesis|journal=Trends in Microbiology|volume=7|issue=5|year=1999|pages=180–182|issn=0966842X|doi=10.1016/S0966-842X(99)01507-3}}</ref>
Protective antigen (PA) and edema factor (EF) combine to form edema toxin (ET), and PA and lethal factor (LF) combine to form lethal toxin (LT). After binding to surface receptors, the PA portion of the complexes facilitates translocation of the [[toxins]] to the [[cytosol]], in which EF and LF exert their toxic effects.<ref name="Moayeri2004">{{cite journal|last1=Moayeri|first1=M|title=The roles of anthrax toxin in pathogenesis|journal=Current Opinion in Microbiology|volume=7|issue=1|year=2004|pages=19–24|issn=13695274|doi=10.1016/j.mib.2003.12.001}}</ref>
[[Bacillus anthracis]] disseminate to multiple organs including [[spleen]], [[liver]], [[intestines]], [[kidneys]], [[adrenal glands]], and [[meninges]], affecting their normal functions and leading to systemic [[infection]] with a potentially fatal outcome.<ref>{{cite book | last = Rubin | first = Raphael | title = Rubin's pathology : clinicopathologic foundations of medicine | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | year = 2012 | isbn = 1605479683 }}</ref><ref>{{cite book | last = Kumar | first = Vinay | title = Robbins and Cotran pathologic basis of disease | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2014 | isbn = 0323266169 }}</ref><ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>


Anthrax is usually contracted by handling infected animals or their wool, germ warfare/terrorism or laboratory accidents.
The [[virulence factors]] of [[Bacillus anthracis]] are:
* [[Antiphagocytic]] [[capsule]]
* [[Toxins]]:
:* PA
:* LF
:* EF


<u>'''1) Pulmonary (pneumonic, respiratory, or inhalation) anthrax'''
===Bacterial Toxins===
</u>
In order to [[infect]] the body, [[Bacillus anthracis]] must produce [[toxins]]. These toxins have 3 main toxic effects: [[edema]], [[hemorrhage]], and [[necrosis]]. Besides their direct [[toxic]] effects responsible for tissue damage, [[anthrax]] [[toxins]] are also responsible for interfering with [[cellular]] pathways, in such way that defense functions of the host's [[immune system]] are affected. This will ultimately allow initial systemic [[infection]] by interfering with the [[immune system]].<ref name="LiuMoayeri2014">{{cite journal|last1=Liu|first1=Shihui|last2=Moayeri|first2=Mahtab|last3=Leppla|first3=Stephen H.|title=Anthrax lethal and edema toxins in anthrax pathogenesis|journal=Trends in Microbiology|volume=22|issue=6|year=2014|pages=317–325|issn=0966842X|doi=10.1016/j.tim.2014.02.012}}</ref>
Respiratory infection initially presents with cold or flu-like symptoms for several days, followed by severe (and often fatal) respiratory collapse. If not treated promptly soon after exposure, before symptoms appear, inhalational anthrax is highly fatal, with near 100% mortality.<ref name="bravata">Bravata DM, Holty JE, Liu H, McDonald KM, Olshen RA, Owens DK (2006), Systematic review: a century of inhalation anthrax cases from 1900 to 2005, Annals of Internal Medicine; 144(4): 270–80.</ref> A lethal dose of anthrax is reported to result from inhalation of about 10,000–20,000 spores. <ref name="urlwww.medicinenet.com">{{cite web |url=http://www.medicinenet.com/script/main/art.asp?articlekey=18812&page=2 |title=www.medicinenet.com |format= |work= |accessdate=2012-08-31}}</ref> Like all diseases there is probably a wide variation to susceptibility with evidence that some people may die from much lower exposures; there is little documented evidence to verify the exact or average number of spores need for infection. Inhalation anthrax is also known as Woolsorters' disease or as Ragpickers' disease since these people often caught it. Other practices associated with exposure include the slicing up of animal horns for the manufacture of buttons, the handling of hair bristles used for the manufacturing of brushes, and the handling of animal skins. Whether these animal skins came from animals that died of the disease or from animals that had simply laid on ground that had spores on it  is unknown. Anthrax is a very hard disease to eliminate since Anthrax spores are devilishly hard to kill and have been known to have reinfected animals over 70 years after burial sites of anthrax infected animals were disturbed. <ref>"Anthrax" by Jeanne Guillemin, University of California Press, 2001,ISBN 0-520-22917-7, pg. 3 </ref>


'''<u>2) Gastrointestinal (gastroenteric) anthrax</u>'''
When isolated, the 3 structural elements of the anthrax [[exotoxins]] are non-toxic. However, when combined, they form [[virulent]] [[exotoxins]]:<ref name="LiuMoayeri2014">{{cite journal|last1=Liu|first1=Shihui|last2=Moayeri|first2=Mahtab|last3=Leppla|first3=Stephen H.|title=Anthrax lethal and edema toxins in anthrax pathogenesis|journal=Trends in Microbiology|volume=22|issue=6|year=2014|pages=317–325|issn=0966842X|doi=10.1016/j.tim.2014.02.012}}</ref>
Gastrointestinal infection is most often caused by eating  anthrax infected meat and is characterized by serious gastrointestinal difficulty, [[vomiting]] of blood, severe diarrhea, acute inflammation of the intestinal tract, and loss of appetite. Gastrointestinal infections can be treated but usually result in fatality rates of 25% to 60%, depending upon how soon treatment commences. <ref>{{cite web | title = Anthrax Q & A: Signs and Symptoms | work = Emergency Preparedness and Response | publisher = Centers for Disease Control and Prevention | date = 2003 | url = http://www.bt.cdc.gov/agent/anthrax/faq/signs.asp | accessdate = 2007-04-19 }}</ref>


<u>'''3) Cutaneous (skin) anthrax'''</u>
* LF + PA = LT (Lethal Toxin)
[[Image:Milzbrand.jpg|thumb|left|250px|Anthrax skin lesion.]]
* EF + PA = ET (Edema Toxin)
Cutaneous (on the skin) anthrax  infection shows up as a boil-like skin lesion that eventually forms an ulcer with a black center (i.e., eschar). The black eschar often shows up as a large, painless necrotic ulcers (beginning as an irritating and itchy skin lesion or blister that is dark and usually concentrated as a black dot, somewhat resembling bread mold) at the site of infection. Cutaneous infections generally form within the site of spore penetration within 2 to 5 days after exposure. Unlike bruises or most other lesions, cutaneous anthrax infections normally  do not cause pain. Cutaneous infection is the least fatal form of anthrax infection if treated. But without treatment, approximately 20% of all cutaneous skin infection cases may progress to [[toxemia]] and death. <ref>{{cite web | title = Anthrax Q & A: Signs and Symptoms | work = Emergency Preparedness and Response | publisher = Centers for Disease Control and Prevention | date = 2003 | url = http://www.bt.cdc.gov/agent/anthrax/faq/signs.asp | accessdate = 2007-04-19 }}</ref> Treated cutaneous anthrax is rarely fatal.<ref name="bravata"/>
 
The PA is responsible for attaching the [[toxin]] to the [[cell]], while the LF and the EF are responsible for the [[toxicity]].<ref name="LiuMoayeri2014">{{cite journal|last1=Liu|first1=Shihui|last2=Moayeri|first2=Mahtab|last3=Leppla|first3=Stephen H.|title=Anthrax lethal and edema toxins in anthrax pathogenesis|journal=Trends in Microbiology|volume=22|issue=6|year=2014|pages=317–325|issn=0966842X|doi=10.1016/j.tim.2014.02.012}}</ref>
 
After germinating, [[B. anthracis]] produces and releases into the [[blood stream]] PA, LF, and EF [[toxins]] separately. However, PA is secreted in its inactivated form (PA). In order to form the [[exotoxin]] complexes with LF and EF, it must first be activated by host-cellular receptors:<ref name="LiuMoayeri2014">{{cite journal|last1=Liu|first1=Shihui|last2=Moayeri|first2=Mahtab|last3=Leppla|first3=Stephen H.|title=Anthrax lethal and edema toxins in anthrax pathogenesis|journal=Trends in Microbiology|volume=22|issue=6|year=2014|pages=317–325|issn=0966842X|doi=10.1016/j.tim.2014.02.012}}</ref>
* CMG2 - ''Capillary Morphogenesis Protein 2'' (predominant toxin receptor''in vivo'')
* TEM8 - ''Tumor Endothelium Marker 8'' (minor role)
 
CMG2 and TEM8 cleave PA into PA20 and PA63. PA63 (a C-terminal fragment) is the activated form of PA, responsible for combining with EF and LF, thereby creating the [[toxin]] [[oligomer]] ''PA63 oligomer receptor complex''. This complex will be internalized via receptor mediated [[endocytosis]] within an [[endosome]].<ref name="LiuMoayeri2014">{{cite journal|last1=Liu|first1=Shihui|last2=Moayeri|first2=Mahtab|last3=Leppla|first3=Stephen H.|title=Anthrax lethal and edema toxins in anthrax pathogenesis|journal=Trends in Microbiology|volume=22|issue=6|year=2014|pages=317–325|issn=0966842X|doi=10.1016/j.tim.2014.02.012}}</ref>
 
The acidic environment within the [[endosomes]] leads to the formation of a channel called ''PA63 oligomer channel'', on the endosomal membrane. LF and EF are then released in the [[cytosol]] of the host [[cell]], to then exert their [[toxic]] effects.<ref name="LiuMoayeri2014">{{cite journal|last1=Liu|first1=Shihui|last2=Moayeri|first2=Mahtab|last3=Leppla|first3=Stephen H.|title=Anthrax lethal and edema toxins in anthrax pathogenesis|journal=Trends in Microbiology|volume=22|issue=6|year=2014|pages=317–325|issn=0966842X|doi=10.1016/j.tim.2014.02.012}}</ref>
 
After experiments in mice, edema toxin was noted to be the major [[virulence factor]] since it caused death of mice in much lesser dosages than lethal toxin.
* Edema toxin is a calmodulin-dependent [[adenylyl cyclase]], known to increase [[intracellular]] [[cAMP]] through the conversion of [[ATP]] into [[cAMP]], thus affecting several [[intracellular]] pathways.
* Lethal toxin is a zinc-dependent metaloproteinase known to interfere with the mitogen-activated protein kinase (MEK), thereby hampering multiple [[intracellular]] mechanisms.<ref name="LiuMoayeri2014">{{cite journal|last1=Liu|first1=Shihui|last2=Moayeri|first2=Mahtab|last3=Leppla|first3=Stephen H.|title=Anthrax lethal and edema toxins in anthrax pathogenesis|journal=Trends in Microbiology|volume=22|issue=6|year=2014|pages=317–325|issn=0966842X|doi=10.1016/j.tim.2014.02.012}}</ref>
 
===Cutaneous or Injection Anthrax===
According to animal studies, [[spores]] that enter the [[skin]] of susceptible animals (either through a lesion or by injection) germinate and give rise, in about 2 - 4 hours, to a small [[edema|edematous]] area containing capsulated [[bacilli]]. The following stages are noticed:<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>
* The lesion increases in size and becomes defined by a zone of altered [[capillaries]] through [[dilatation]], [[congestion]], and [[swelling]] of the [[endothelial cells]] and through [[diapedesis]] of [[neutrophils]].
* [[Macrophages]] and [[fibrin]] deposits appear, and the efferent [[lymphatics]] become dilated.
* Continued multiplication of the [[bacilli]] in the lesion leads to fragmentation of the [[connective tissue]], as the [[edema]] spreads extensively away from the [[infection]] site.
* [[Necrosis]] and [[hemorrhage]] occur. If initial [[inoculation]] has happened with minimal number of [[spores]], the primary lesion may be insignificant compared with that of the draining [[lymph node]]s.
* The [[bacilli]] migrate from the primary lesion, by means of the [[lymph vessel]]s, to the local [[lymph nodes]] where multiplication occurs, releasing a continuous stream of organisms and [[toxins]] into the efferent [[lymph vessel]]s and to the [[spleen]] and other lymphoid tissues where multiplication continues.
* In animals who died following [[subcutaneous]] challenge, the local [[lymph node]]s became [[hemorrhage|haemorrhagic]] and [[edema|edematous]]. [[Necrosis]] of lymphatic elements and of [[blood vessel]] walls occur and [[phagocytosis]] of the [[bacilli]] is apparent.
*  [[Septicemia]] often courses with [[splenic]] enlargement
 
Injection anthrax will have similar [[pathogenesis]] to cutaneous anthrax, but since it is injected, it can spread throughout the body faster and it becomes harder to recognize and treat than the [[cutaneous]] form.<ref name=CDC>{{cite web | title = Anthrax Symptoms | url = http://www.cdc.gov/anthrax/basics/symptoms.html }}</ref>
 
===Inhalation Anthrax===
In inhalation anthrax, the inhaled [[spores]] will be deposited in the [[alveoli]] first. From there, they will be transported, within [[phagocytic cells]], through the [[lymphatic vessel]]s to the [[mediastinal]] [[lymph node]]s, where they will grow and cause [[hemorrhage|hemorrhagic]] [[lymphadenitis]]. [[Bacillus anthracis|Bacteria]] escape from the damaged [[lymph node]]s and invade the [[blood stream]] via the [[thoracic duct]]. Vegetative [[Bacillus]] then travel through the [[bloodstream]] and [[lymph vessel]]s, potentially causing [[septicemia]]. At the same time [[toxins]] are released, causing tissue damage and hampering the [[immune system]] to facilitate [[bacterial]] spread.<ref>{{cite book | last = Turnbull | first = Peter | title = Anthrax in humans and animals | publisher = World Health Organization | location = Geneva, Switzerland | year = 2008 | isbn = 9789241547536 }}</ref><ref name="pmid12610093">{{cite journal| author=Spencer RC| title=Bacillus anthracis. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 3 | pages= 182-7 | pmid=12610093 | doi= | pmc=PMC1769905 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12610093  }} </ref><ref name="pmid8486963">{{cite journal| author=Friedlander AM, Welkos SL, Pitt ML, Ezzell JW, Worsham PL, Rose KJ et al.| title=Postexposure prophylaxis against experimental inhalation anthrax. | journal=J Infect Dis | year= 1993 | volume= 167 | issue= 5 | pages= 1239-43 | pmid=8486963 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8486963  }} </ref>
 
Once the [[bacteremia]] and associated [[toxemia]] reach a critical level, the severe [[symptoms]] that are characteristic of the acute phase of illness are manifested. During the acute phase, damage of the [[lung]] tissue becomes apparent on the [[X-ray]]. This damage results from the action of [[anthrax toxin]] on the [[endothelium]] of the lung’s [[capillary bed]]. Primary damage of the [[lung]] is not normally a feature of the initial phase of illness and primary [[pulmonary]] [[infection]] is an uncommon presentation.<ref>{{cite book | last = Turnbull | first = Peter | title = Anthrax in humans and animals | publisher = World Health Organization | location = Geneva, Switzerland | year = 2008 | isbn = 9789241547536 }}</ref><ref name="pmid12610093">{{cite journal| author=Spencer RC| title=Bacillus anthracis. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 3 | pages= 182-7 | pmid=12610093 | doi= | pmc=PMC1769905 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12610093  }} </ref><ref name="pmid8486963">{{cite journal| author=Friedlander AM, Welkos SL, Pitt ML, Ezzell JW, Worsham PL, Rose KJ et al.| title=Postexposure prophylaxis against experimental inhalation anthrax. | journal=J Infect Dis | year= 1993 | volume= 167 | issue= 5 | pages= 1239-43 | pmid=8486963 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8486963  }} </ref>
 
Studies in rhesus monkeys revealed that after [[spore]] [[inhalation]], its germination might take up to 60 days. This is the reason why [[antibiotic]] [[prophylaxis]] is recommended for 60 days.<ref name="pmid12610093">{{cite journal| author=Spencer RC| title=Bacillus anthracis. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 3 | pages= 182-7 | pmid=12610093 | doi= | pmc=PMC1769905 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12610093  }} </ref>
 
===Gastrointestinal Anthrax===
In animal studies, the [[intestinal]] lesions caused by ingested anthrax [[spores]] range from focal to diffuse [[hemorrhage|hemorrhagic]] [[necrotic]] [[enteritis]] of the [[small intestine]]. The tendency for localized lesions to develop in [[Peyer's patches]] suggests a possible role of the [[M cell]] in the uptake of the anthrax [[bacillus]].<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref>
 
==Gross Pathology==
===Cutaneous and Injection Anthrax===
[[Cutaneous]] [[infection]] typically produces [[ulcer|ulcerated]] lesions which are covered by a scab and often contain numerous [[microorganisms]]. Anthrax [[eschar]]s are generally seen on exposed unprotected regions of the body, mostly on the [[face]], [[neck]], [[hands]] and [[wrist]]s. Generally [[cutaneous]] lesions are single, but sometimes two or more lesions are present.<ref>{{cite book | last = Rubin | first = Raphael | title = Rubin's pathology : clinicopathologic foundations of medicine | publisher = Wolters Kluwer Health/Lippincott Williams & Wilkins | location = Philadelphia | year = 2012 | isbn = 1605479683 }}</ref><ref>{{cite book | last = Kumar | first = Vinay | title = Robbins and Cotran pathologic basis of disease | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2014 | isbn = 0323266169 }}</ref>
 
The lesions produced by injection anthrax will be similar to the ones of the [[cutaneous]] form. The difference will reside on the fact that injection anthrax can spread throughout the body faster and be harder to recognize and treat than cutaneous anthrax.<ref name=CDC>{{cite web | title = Anthrax Symptoms | url = http://www.cdc.gov/anthrax/basics/symptoms.html }}</ref>
 
===Inhalational Anthrax===   
Gross pathologic lesions observed in non-human primates used in aerosol challenge models of inhalation anthrax include [[edema]], [[congestion]], [[hemorrhage]], and [[necrosis]] in the [[lungs]] and [[mediastinum]]. [[Splenitis]] and [[necrotizing]] or [[hemorrhage|hemorrhagic]] [[lymphadenitis]] involving the [[mediastinal]], [[tracheobronchial]], and other [[lymph nodes]] are common.<ref name="GuarnerJernigan2003">{{cite journal|last1=Guarner|first1=Jeannette|last2=Jernigan|first2=John A.|last3=Shieh|first3=Wun-Ju|last4=Tatti|first4=Kathleen|last5=Flannagan|first5=Lisa M.|last6=Stephens|first6=David S.|last7=Popovic|first7=Tanja|last8=Ashford|first8=David A.|last9=Perkins|first9=Bradley A.|last10=Zaki|first10=Sherif R.|title=Pathology and Pathogenesis of Bioterrorism-Related Inhalational Anthrax|journal=The American Journal of Pathology|volume=163|issue=2|year=2003|pages=701–709|issn=00029440|doi=10.1016/S0002-9440(10)63697-8}}</ref> Primary [[pulmonary]] lesions, including those of [[pneumonia]], are occasionally observed. [[Meningeal]] involvement ranging from [[edema]], [[congestion]], [[hemorrhage]], and [[necrosis]] to [[suppurative]] or [[hemorrhage|hemorrhagic]] [[meningitis]], usually secondary to hematogenous spread from other types of [[anthrax]], occurs in ≤77% of animals studied.<ref name="Twenhafel2010">{{cite journal|last1=Twenhafel|first1=N. A.|title=Pathology of Inhalational Anthrax Animal Models|journal=Veterinary Pathology|volume=47|issue=5|year=2010|pages=819–830|issn=0300-9858|doi=10.1177/0300985810378112}}</ref> Autopsy findings from persons who died from inhalation anthrax in Sverdlovsk and in the United States<ref>{{Cite journal| author = [[A. A. Abramova]] & [[L. M. Grinberg]] | title = &#91;Pathology of anthrax sepsis according to materials of the infectious outbreak in 1979 in Sverdlovsk (macroscopic changes)&#93; | journal = [[Arkhiv patologii]] | volume = 55 | issue = 1 | pages = 12–17 | year = 1993 | month = January-February | pmid = 7980032}}</ref> are consistent with findings from the non-human primates studies. Persons who died had extensive amounts of serosanguinous fluid in [[pleural]] cavities, [[edema]], and [[hemorrhage]] of the [[mediastinum]] and surrounding soft tissues. 48% had cerebral [[edema]], 21% had [[ascites]], 17% had [[pericardial effusion]]s, and 14% had [[petechial rash]]. [[Mediastinal]] [[lymph nodes]] and [[spleen]] also showed [[hemorrhage]] and [[necrosis]].<ref name="GuarnerJernigan2003">{{cite journal|last1=Guarner|first1=Jeannette|last2=Jernigan|first2=John A.|last3=Shieh|first3=Wun-Ju|last4=Tatti|first4=Kathleen|last5=Flannagan|first5=Lisa M.|last6=Stephens|first6=David S.|last7=Popovic|first7=Tanja|last8=Ashford|first8=David A.|last9=Perkins|first9=Bradley A.|last10=Zaki|first10=Sherif R.|title=Pathology and Pathogenesis of Bioterrorism-Related Inhalational Anthrax|journal=The American Journal of Pathology|volume=163|issue=2|year=2003|pages=701–709|issn=00029440|doi=10.1016/S0002-9440(10)63697-8}}</ref><ref>{{Cite journal| author = [[A. A. Abramova]] & [[L. M. Grinberg]] | title = &#91;Pathology of anthrax sepsis according to materials of the infectious outbreak in 1979 in Sverdlovsk (macroscopic changes)&#93; | journal = [[Arkhiv patologii]] | volume = 55 | issue = 1 | pages = 12–17 | year = 1993 | month = January-February | pmid = 7980032}}</ref>
 
===Gastrointestinal Anthrax===
On [[gastrointestinal]] [[infection]] the typical [[eschar]] may occur on different locations, including:<ref name="pmid12610093">{{cite journal| author=Spencer RC| title=Bacillus anthracis. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 3 | pages= 182-7 | pmid=12610093 | doi= | pmc=PMC1769905 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12610093  }} </ref>
* [[Oropharynx]]
* [[Stomach]]
* [[Duodenum]]
* [[Ileum]]
* [[Cecum]]
According to the location of the [[eschar]], gastrointestinal anthrax may be divided in 2 categories: [[oropharyngeal]] and [[abdominal]].<ref name="pmid12610093">{{cite journal| author=Spencer RC| title=Bacillus anthracis. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 3 | pages= 182-7 | pmid=12610093 | doi= | pmc=PMC1769905 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12610093  }} </ref>
 
As the [[eschar]] progresses, [[symptoms]] will appear as a result of the [[necrosis]] of the lesion, coupled with severe [[intestinal]] and [[mesenteric]] [[edema]] and [[lymph node]] enlargement in the [[mesentery]].<ref name="pmid12610093">{{cite journal| author=Spencer RC| title=Bacillus anthracis. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 3 | pages= 182-7 | pmid=12610093 | doi= | pmc=PMC1769905 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12610093  }} </ref>
 
==Microscopic Pathology==
Anthrax lesions at any site are characterized by extensive [[necrosis]] and confluent [[exudate]], containing [[macrophages]] and [[neutrophils]]. In [[histopathological]] specimens or culture media, the presence of large boxcar-shaped [[Gram-positive]] [[bacilli]] in chains suggests the [[diagnosis]].
 
===Cutaneous or Injection Anthrax===
[[Histologic]] examination of [[skin lesions]] caused by cutaneous anthrax reveals:<ref name="DixonMeselson1999">{{cite journal|last1=Dixon|first1=Terry C.|last2=Meselson|first2=Matthew|last3=Guillemin|first3=Jeanne|last4=Hanna|first4=Philip C.|title=Anthrax|journal=New England Journal of Medicine|volume=341|issue=11|year=1999|pages=815–826|issn=0028-4793|doi=10.1056/NEJM199909093411107}}</ref>
* Tissue [[necrosis]]
* [[Edema]]
* [[Lymphocytic]] infiltrates
* No [[liquefaction]]
* No [[abscess]] formation (lesion is not [[suppurative]])
* Focal points of [[hemorrhage]]
* [[Thrombosis]]
* [[Bacilli]] in [[subcutaneous]] tissue, revealed by [[Gram staining]]
 
===Inhalation Anthrax===
Histologic evaluation of affected tissues reveals:
* Numerous [[necrotic]] foci of [[hemorrhage]] in the [[mediastinum]] or [[hilar]] and peribronchial [[lymph nodes]]
* [[Pulmonary]] [[infection]] may also result in interstitial [[pneumonia]] associated with:
:* [[Vasculitis]]
:* [[Edema]]
:* Infiltrating [[macrophages]] and [[neutrophils]]
* [[Bacilli]] are most likely to be observed in the [[alveolar]] [[capillaries]] and [[venules]] and, to a lesser degree, within the [[alveolar]] space and draining [[lymph nodes]]
 
===Gastrointestinal Anthrax===
[[Histologic]] evaluation of affected tissues revealed:<ref name="DixonMeselson1999">{{cite journal|last1=Dixon|first1=Terry C.|last2=Meselson|first2=Matthew|last3=Guillemin|first3=Jeanne|last4=Hanna|first4=Philip C.|title=Anthrax|journal=New England Journal of Medicine|volume=341|issue=11|year=1999|pages=815–826|issn=0028-4793|doi=10.1056/NEJM199909093411107}}</ref>
* [[Edema]]
* [[Mucosal]] [[necrosis]]
* [[Inflammatory]] infiltrates
* [[Peritoneal fluid]] may reveal [[gram-positive]] [[bacilli]]
* Occasionally [[mediastinal]] widening
 
==Gallery==
<gallery>
Image:CutaneousA6.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Sterne strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on sheep blood agar (SBA) medium, for a 48 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA7.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Sterne strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on sheep blood agar (SBA) medium, for a 24 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA8.jpg| Low-power magnification of 5X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Sterne strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on sheep blood agar (SBA) medium, for a 24 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA9.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Sterne strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on polymyxin B - lysozyme - EDTA – thallous acetate agar (PLET) medium, for a 24 hour time period, at a temperature of 37°C”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA10.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Sterne strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on phenylethyl alcohol agar (PEA) medium, for a 48 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA11.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Sterne strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on phenylethyl alcohol agar (PEA) medium, for a 24 hour time period, at a temperature of 37°.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA12.jpg| Low-power magnification of 5X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Sterne strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on phenylethyl alcohol agar (PEA) medium, for a 24 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA13.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Sterne strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on mannitol, egg yolk, polymyxin agar (MEP) medium, for a 24 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA14.jpg| Low-power magnification of 5X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Sterne strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on mannitol, egg yolk, polymyxin agar (MEP) medium, for a 24 hour time period, at a temperature of 37°C. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA15.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Sterne strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on colistin-naladixic acid agar (CNA) medium, for a 48 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA16.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Sterne strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on colistin-naladixic acid agar (CNA) medium, for a 24 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA17.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Sterne strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on mannitol, egg yolk, polymyxin agar (MEP) medium, for a 48 hour time period, at a temperature of 37°C. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA18.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on polymyxin B - lysozyme - EDTA – thallous acetate agar (PLET) medium, for a 48 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA19.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on sheep blood agar (SBA) medium, for a 48 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA20.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on sheep blood agar (SBA) medium, for a 24 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA21.jpg| Low-power magnification of 5X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on sheep blood agar (SBA) medium, for a 24 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA22.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on polymyxin B - lysozyme - EDTA – thallous acetate agar (PLET) medium, for a 48 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA23.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on polymyxin B - lysozyme - EDTA – thallous acetate agar (PLET) medium, for a 24 hour time period, at a temperature of 37°C. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA24.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on phenylethyl alcohol agar (PEA) medium, for a 48 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA25.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on phenylethyl alcohol agar (PEA) medium, for a 48 hour time period, at a temperature of 37°C. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA26.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on phenylethyl alcohol agar (PEA) medium, for a 24 hour time period, at a temperature of 37°C. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA27.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on phenylethyl alcohol agar (PEA) medium, for a 24 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA28.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on mannitol, egg yolk, polymyxin agar (MEP) medium, for a 48 hour time period, at a temperature of 37°C. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA29.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on colistin-naladixic acid agar (CNA) medium, for a 48 hour time period, at a temperature of 37°C. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA30.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on colistin-naladixic acid agar (CNA) medium, for a 24 hour time period, at a temperature of 37°C. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA31.jpg| Low-power magnification of 10X of a digital Keyence scope, this photograph depicts the colonial growth displayed by Pasteur strain members of the Gram-positive bacterium, Bacillus anthracis, which were cultured on colistin-naladixic acid agar (CNA) medium, for a 24 hour time period, at a temperature of 37°C. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA32.jpg| Magnification of 10X, this image depicts a number of Gram-positive Bacillus anthracis bacterial colonies of the Sterne-strain, which had been cultivated on a blood agar plate (BAP), and incubated for a 24 hour time period at a temperature of 35 °C. Of particular note was the classic “ground glass” texture exhibited by the colonies, resembling a pile of glass shards. As they continued to grow, and their edges touched, you can see that these colonies had coalesced, destroying their originally well-demarcated borders.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA33.jpg| Magnification of 10X, this image depicts a number of Gram-positive Bacillus anthracis bacterial colonies of the Sterne-strain, which had been cultivated on a blood agar plate (BAP), and incubated for a 24 hour time period at a temperature of 35 °C. Of particular note was the classic “ground glass” texture exhibited by the colonies, resembling a pile of glass shards. As they continued to grow, and their edges touched, you can see that these colonies had coalesced, destroying their originally well-demarcated borders.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA34.jpg| Magnification of 30X, this image depicts a single Gram-positive Bacillus anthracis bacterial colony of the Sterne-strain, which had been cultivated on a blood agar plate (BAP), and incubated for a 24 hour time period at a temperature of 35 °C. Of particular note was the classic “ground glass” texture exhibited by the colony, resembling a pile of glass shards. In the background, you’ll note that as these colonies continued to grow, and their edges touched, they coalesced, destroying their originally well-demarcated borders.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA35.jpg| Magnification of 20X, this image depicts a number of Gram-positive Bacillus anthracis bacterial colonies of the Sterne-strain, which had been cultivated on a blood agar plate (BAP), and incubated for a 24 hour time period at a temperature of 35 °C. Of particular note was the classic “ground glass” texture exhibited by the colonies, resembling a pile of glass shards. As they continued to grow, and their edges touched, you can see that these colonies had coalesced, destroying their originally well-demarcated borders.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA36.jpg| Hematoxylin-eosin-stained (H&E) photomicrograph of a tissue specimen harvested from the bronchus of a deceased 60 year-old man, revealed cytoarchitectural changes associated with a case of inhalation anthrax, due to Gram-positive Bacillus anthracis bacteria.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA37.jpg| Colonial morphology displayed by Gram-positive, Pasteur strain, Bacillus anthracis bacteria, which was grown on a medium of phenylethyl alcohol agar (PEA), for a 24 hour time period, at a temperature of 37°C”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA38.jpg| Colonial morphology displayed by Gram-positive, Pasteur strain, Bacillus anthracis bacteria, which was grown on a medium of phenylethyl alcohol agar (PEA), for a 24 hour time period, at a temperature of 37°C. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA39.jpg| Light colonial growth displayed by Gram-positive, Pasteur strain, Bacillus anthracis bacteria, which was grown on a medium of MacConkey agar, for a 24 hour time period, at a temperature of 37°C. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA40.jpg| Light colonial growth displayed by Gram-positive, Pasteur strain, Bacillus anthracis bacteria, which was grown on a medium of MacConkey agar, for a 24 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA41A.png| Light colonial growth displayed by Gram-positive, Pasteur strain, Bacillus anthracis bacteria, which was grown on a medium of CNA agar, for a 24 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA42.jpg| Light colonial growth displayed by Gram-positive, Pasteur strain, Bacillus anthracis bacteria, which was grown on a medium of CNA agar, for a 24 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA43.jpg| Colonial morphology displayed by Gram-positive, Pasteur strain, Bacillus anthracis bacteria, which was grown on a medium of chocolate agar, for a 24 hour time period, at a temperature of 37°C.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA44.jpg| Bacillus anthracis bacterial colonies, which had been allowed to grow on sheep’s blood agar (SBA) for a 24 hour period. In this particular view you’ll note the appearance of what is termed a "plaque" (arrowhead), which represents an area where the bacteria had been lysed, or destroyed by the application of a localized amount of gamma phage-containing solution. Highly specific toB. anthracis, these gamma phage viruses, i.e., bacteriophages, attacked the B. anthracis bacteria, subsequently leaving this circular plaque devoid of bacterial organisms. The specificity of these gamma phages to B. anthracis makes this a positive test for the presence of this bacterium.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA45.jpg| Bacillus anthracis bacterial colonies, which had been allowed to grow on sheep’s blood agar (SBA) for a 24 hour period. Note the classical appearance exhibited in the colonial morphology including a ground-glass, non-pigmented texture with accompanying “comma” projections from some of the individual rough-edged colonies. In this particular view, you’ll note that a “tenacity test” had been performed using an iinoculating loop, which proved positive for B. anthracis, causing the “colony to ‘stand up’ like beaten egg white”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA46.jpg| Bacillus anthracis bacterial colonies, which have been allowed to grow on sheep’s blood agar (SBA) for a 24 hour period. Note the classical appearance exhibited in the colonial morphology including a ground-glass, non-pigmented texture with accompanying “comma” projections from some of the individual rough-edged colonies. In this particular view, you’ll note that a “tenacity test” had been performed using an iinoculating loop, which proved positive for B. anthracis, causing the “colony to ‘stand up’ like beaten egg white”.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA47.jpg| Bacillus anthracis bacterial colonies, which have been allowed to grow on sheep’s blood agar (SBA) for a 24 hour period. Note the classical appearance exhibited in the colonial morphology including a ground-glass, non-pigmented texture with accompanying “comma” projections from some of the individual rough-edged colonies. In this particular view, you’ll note that a “tenacity test” had been performed using an iinoculating loop, which proved positive for B. anthracis, causing the “colony to ‘stand up’ like beaten egg white”.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA48.jpg| Bacillus anthracis bacterial colonies, which have been allowed to grow on sheep’s blood agar (SBA) for a 24 hour period. Note the classical appearance exhibited in the colonial morphology including a ground-glass, non-pigmented texture with accompanying “comma” projections from some of the individual rough-edged colonies.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA49.jpg| Bacillus anthracis bacterial colonies, which have been allowed to grow on sheep’s blood agar (SBA) for a 24 hour period. Note the classical appearance exhibited in the colonial morphology including a ground-glass, non-pigmented texture with accompanying “comma” projections from some of the individual rough-edged colonies. See PHIL 11748 for a higher magnification of these colonies.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA50.jpg| Magnification of 6,408X, this scanning electron micrograph (SEM) depicted spores from the Aimes strain of Bacillus anthracis bacteria. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA51.jpg| Magnification of 31,207X, this scanning electron micrograph (SEM) depicted spores from the Sterne strain of Bacillus anthracis bacteria. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:AnthraxCauses1.jpg| Magnification of 12,483X, this scanning electron micrograph (SEM) depicted spores from the Sterne strain of Bacillus anthracis bacteria.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA53.jpg| Gram-positive, endospore-forming Bacillus anthracisbacteria. B. anthracis is the pathologic microorganism responsible for the disease “anthrax”, an acute infectious disease, which most commonly occurs in wild and domestic vertebrates (cattle, sheep, goats, camels, antelopes, and other herbivores), but it can also occur in humans when they are exposed to infected animals, or tissue from infected animals.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA54.jpg| Gross pathologic posterior oblique view of a chimpanzee's lungs that had contracted fatal inhalation anthrax.” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA55.jpg| Micrograph revealing submucosal hemorrhage in the small intestine, in a case of fatal human anthrax; H&E stain; Mg. 240X.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA56.jpg| Micrograph revealing submucosal hemorrhage in the small intestine, in a case of fatal human anthrax; H&E stain; Mg. 240X.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA57.jpg| "Meningeal infection due to Bacillus anthracis bacteria using an H&E stain” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA63.jpg| "Blood agar culture plate growing B. anthracis and other soil flora.” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA65.jpg| Brain section through the ventricles revealing an inter ventricular hemorrhage as consequence of virulence factors of Bacillus anthracis (edema toxin, lethal toxin, and antiphagocytic capsular antigen). The toxins are responsible for the primary clinical manifestations of hemorrhage, edema, and necrosis”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA66.jpg| Agar culture plate is growing Bacillus anthracis colonies.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA67.jpg| Blood agar culture plate growing B. anthracis and other soil flora.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA68.jpg| Cutaneous anthrax lesion on the arm of a 50 year old female.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA70.jpg| "Magnification of 12,483X, this scanning electron micrograph (SEM) depicted spores from the Sterne strain of Bacillus anthracis bacteria. ”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA71.jpg| "Magnification of 12,483X, this scanning electron micrograph (SEM) depicted spores from the Sterne strain of Bacillus anthracis bacteria.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA72.jpg| "Magnification of 6,408X, this scanning electron micrograph (SEM) depicted spores from the Aimes strain of Bacillus anthracis bacteria.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:Bacillus anthracis Gram.jpg| "Photomicrograph of Bacillus anthracis bacteria using Gram-stain technique”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA74.jpg| "Bacillus anthracis taken from the peritoneum using a Hiss capsule stain.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA75.jpg| "Photomicrograph of Bacillus anthracis bacteria taken from heart blood, and using Carbol Fuchsin stain.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA76.jpg| "Bacillus anthracis positive encapsulation test is demonstrated using two different agar media”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA77.jpg| "Photomicrograph demonstrating a positive Gram stain with Bacillus anthracis”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA80.jpg| "Bacillus anthracis tenacity positive on sheep blood agar.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA81.jpg| "Bacillus anthracis tenacity positive on sheep blood agar”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA82.jpg| "Bacillus anthracis tenacity positive on sheep blood agar”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA83.jpg| "Bacillus anthracis Avirulent Pasteur Strain, Non-hemolytic on sheep blood agar” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousAA84.jpg| "Bacillus anthracis spores seen under phase contrast microscopy”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA85.jpg| "Bacillus anthracis spores seen under phase contrast microscopy”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA86.jpg| "Bacillus anthracis spores seen under phase contrast microscopy”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA87.jpg| "Bacillus anthracis spores seen under phase contrast microscopy”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA88.jpg| "B. anthracis Direct Fluorescent Antibody (DFA) capsule stain”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA89.jpg| "B. anthracis Direct Fluorescent Antibody (DFA) capsule stain.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA90.jpg| "B. anthracis Direct Fluorescent Antibody (DFA) capsule stain.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA91.jpg| "B. anthracis Direct Fluorescent Antibody (DFA) cell wall stain.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA92.jpg| "B. anthracis Direct Fluorescent Antibody (DFA) cell wall stain.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:Cutaneous93.jpg| "Bacillus anthracis gamma phage lysis on sheep blood agar.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA94.jpg| "Bacillus anthracis Indian Ink capsule stain.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA95.jpg| "Bacillus anthracis M'Fadyean capsule stain”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA96.jpg| "Bacillus anthracis capsule production on bicarbonate agar medium”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA97.jpg| "Hemorrhagic lymph node due to inhalation anthrax”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA98.jpg| "Transmission electron micrograph of Bacillus anthracis.” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA99.jpg| "Transmission electron micrograph of Bacillus anthracis”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA100.jpg| "Transmission electron micrograph of Bacillus anthracis”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA101.jpg| "Transmission electron micrograph of Bacillus anthracis.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA102.jpg| "Transmission electron micrographic image of Bacillus anthracis”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA93A.jpg| "Transmission electron micrograph of Bacillus anthracis”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA104.jpg| "Confocal micrograph of Bacillus anthracis”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA105.jpg| "Numerous rod-shaped Bacillus anthracis bacteria, some that had linked together to form chains, while others remained solitary”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA108.jpg| "Necrosis of lymph node due to anthrax”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA120.jpg| "Bacillus anthracis from agar culture <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA121.jpg| "Photomicrograph of meninges demonstrating the presence of Bacillus anthracis in a case of fatal inhalation anthrax.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA122.jpg| "Photomicrograph of lung tissue demonstrating pneumonia in a case of fatal human inhalation anthrax<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA123.jpg| "Bacillus anthracis in lung <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA124.jpg| "Meningeal hemorrhage due to anthrax”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA125.jpg| "Photomicrograph of meninges demonstrating hemorrhage due to fatal inhalation anthrax”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA126.jpg| "Severe hemorrhagic necrosis of lymph node due to anthrax”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA127.jpg| "Mild meningitis with hemorrhage due to Bacillus anthracis”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA128.jpg| "Photomicrograph of serohemorrhagic meningitis in a case of fatal human anthrax with the presence ofBacillus anthracis.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA129.jpg| "Blood agar plate culture of Bacillus anthracis, with a positive gamma phage test”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA130.jpg| "Sheep blood agar plate culture of Bacillus anthracis and Bacillus cereus”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA131.jpg| "Gross pathology of fixed, cut brain showing hemorrhagic meningitis due to inhalation anthrax.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA132.jpg| "Gross pathology of fixed, cut brain showing hemorrhagic meningitis due to inhalation anthrax.”<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA135.jpg| "Gram-stained photomicrograph revealing numerous rod-shaped Bacillus anthracis bacteria that had linked together to form long filamentous chains.” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA136.jpg| "Gram-stained photomicrograph revealing numerous rod-shaped Bacillus anthracis bacteria that had linked together to form long filamentous chains.” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA137.jpg| "Hematoxylin-eosin (H&E)-stained photomicrograph of a small intestinal tissue sample revealed the presence of histopathologic changes indicative of marked mucosal and submucosal hemorrhage, with accompanying arteriolar degeneration in a case of fatal human anthrax.” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA138.jpg| "Hematoxylin-eosin (H&E)-stained photomicrograph of a meningeal tissue sample revealed the presence of histopathologic changes indicative of hemorrhagic meningitis in a case of fatal human anthrax.”  <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA139.jpg| "Histopathology of mediastinal lymph node in fatal human anthrax” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA140.jpg| "Histopathology of mediastinal lymph node in fatal human anthrax” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA141.jpg| "Hematoxylin-eosin (H&E)-stained photomicrograph of a mediastinal lymph node tissue sample revealed the presence of histopathologic changes indicative of an occluded blood vessel in a case of fatal human anthrax.” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA142.jpg| "Hematoxylin-eosin (H&E)-stained photomicrograph of a mediastinal lymph node tissue sample revealed the presence of histopathologic changes indicative of medullary hemorrhage and necrosis in a case of fatal human anthrax.<SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA144.jpg| "Hematoxylin-eosin (H&E)-stained photomicrograph of a mediastinal lymph node tissue sample revealed the presence of histopathologic changes indicative of medullary necrosis in a case of fatal human anthrax.” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
Image:CutaneousA145.jpg| "Under a relatively-low magnification of 96X, this hematoxylin-eosin (H&E)-stained photomicrograph of a mediastinal lymph node tissue sample revealed the presence of histopathologic changes indicative of medullary necrosis in a case of fatal human anthrax.” <SMALL><SMALL>''[http://phil.cdc.gov/phil/  Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL>
 
</gallery>


==References==
==References==
Line 39: Line 369:
{{WikiDoc Help Menu}}
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
{{WikiDoc Sources}}
[[Category:Disease]]
[[Category:Bacterial diseases]]
[[Category:Biological weapons]]
[[Category:Livestock]]
[[Category:Zoonoses]]
[[Category:Medical disasters]]
[[Category:Emergency mdicine]]
[[Category:Up-To-Date]]
[[Category:Infectious disease]]
[[Category:Dermatology]]
[[Category:Pulmonology]]
[[Category:Gastroenterology]]

Latest revision as of 20:25, 29 July 2020

Anthrax Microchapters

Home

Patient Information

Overview

Historical Perspective

Pathophysiology

Causes

Differentiating Anthrax from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

CT

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Anthrax pathophysiology On the Web

Most recent articles

cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Anthrax pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Anthrax pathophysiology

CDC on Anthrax pathophysiology

Anthrax pathophysiology in the news

Blogs on Anthrax pathophysiology

Directions to Hospitals Treating Anthrax

Risk calculators and risk factors for Anthrax pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

The genetic material of Bacillus anthracis is coded within 1 chromosome and 2 plasmids, which are fundamental for its toxicity. The spores of B. anthracis are the infectious form and can remain dormant in the environment for decades. The disease may be transmitted through the skin, gastrointestinal or respiratory systems. The bacterium causes disease through 2 mechanisms: toxemia and bacterial infection.[1] B. anthracis begins to produce toxins within hours of germination.[2] Protective antigen (PA) and edema factor (EF) combine to form edema toxin (ET), and PA and lethal factor (LF) combine to form lethal toxin (LT), the active toxins. Bacterial toxins have a direct cytotoxic effect by interfering with cellular pathways, being also responsible for weakening the immune system, so the initial systemic infection may occur. Anthrax lesions at any site are characterized by lymphadenopathy, extensive edema, necrosis and confluent exudate containing macrophages and neutrophils. If not stopped, the infection may affect different organs, causing septicemia and potentially death.

Genetics

The genetic component of Bacillus anthracis includes 1 chromosome and 2 plasmids. These plasmids (pXO1 and pXO2) are fundamental for its toxicity:[1]

  • pXO1 - encodes 3 components of the anthrax exotoxins:
  • Protective Antigen (PA)
  • Lethal Factor (LF)
  • Edema Factor (EF)

Transmission

The route of transmission of anthrax allows for its classification into the following:[3]

  • Cutaneous anthrax - commonly requires a prior skin lesion as a prerequisite for infection
  • Gastrointestinal anthrax - contracted following ingestion of contaminated food, primarily meat from an animal that died of the disease, or conceivably from ingestion of contaminated water
  • Inhalational anthrax - from breathing in airborne anthrax spores
  • Injection anthrax - from the injection of a drug containing or contaminated with Bacillus anthracis

Pathogenesis

B. anthracis, the causative agent of anthrax, is a spore-forming bacterium. The spores of B. anthracis, which can remain dormant in the environment for decades, are the infectious form, but this vegetative form of B. anthracis rarely causes disease.[4] The bacterium causes disease through 2 mechanisms: toxemia and bacterial infection.[1] Spores introduced through the skin lead to cutaneous or injection anthrax; those introduced through the gastrointestinal tract lead to gastrointestinal anthrax; and those introduced through the lungs lead to inhalation anthrax. After entering a human or animal, B. anthracis spores are believed to germinate locally or be phagocytosed by dendritic cells and macrophages. These will then carry the spores to the lymph nodes, where they germinate.[5][1] B. anthracis begins to produce toxins within hours of germination.[2] Protective antigen (PA) and edema factor (EF) combine to form edema toxin (ET), and PA and lethal factor (LF) combine to form lethal toxin (LT). After binding to surface receptors, the PA portion of the complexes facilitates translocation of the toxins to the cytosol, in which EF and LF exert their toxic effects.[6] Bacillus anthracis disseminate to multiple organs including spleen, liver, intestines, kidneys, adrenal glands, and meninges, affecting their normal functions and leading to systemic infection with a potentially fatal outcome.[7][8][3]

The virulence factors of Bacillus anthracis are:

  • PA
  • LF
  • EF

Bacterial Toxins

In order to infect the body, Bacillus anthracis must produce toxins. These toxins have 3 main toxic effects: edema, hemorrhage, and necrosis. Besides their direct toxic effects responsible for tissue damage, anthrax toxins are also responsible for interfering with cellular pathways, in such way that defense functions of the host's immune system are affected. This will ultimately allow initial systemic infection by interfering with the immune system.[1]

When isolated, the 3 structural elements of the anthrax exotoxins are non-toxic. However, when combined, they form virulent exotoxins:[1]

  • LF + PA = LT (Lethal Toxin)
  • EF + PA = ET (Edema Toxin)

The PA is responsible for attaching the toxin to the cell, while the LF and the EF are responsible for the toxicity.[1]

After germinating, B. anthracis produces and releases into the blood stream PA, LF, and EF toxins separately. However, PA is secreted in its inactivated form (PA). In order to form the exotoxin complexes with LF and EF, it must first be activated by host-cellular receptors:[1]

  • CMG2 - Capillary Morphogenesis Protein 2 (predominant toxin receptorin vivo)
  • TEM8 - Tumor Endothelium Marker 8 (minor role)

CMG2 and TEM8 cleave PA into PA20 and PA63. PA63 (a C-terminal fragment) is the activated form of PA, responsible for combining with EF and LF, thereby creating the toxin oligomer PA63 oligomer receptor complex. This complex will be internalized via receptor mediated endocytosis within an endosome.[1]

The acidic environment within the endosomes leads to the formation of a channel called PA63 oligomer channel, on the endosomal membrane. LF and EF are then released in the cytosol of the host cell, to then exert their toxic effects.[1]

After experiments in mice, edema toxin was noted to be the major virulence factor since it caused death of mice in much lesser dosages than lethal toxin.

  • Edema toxin is a calmodulin-dependent adenylyl cyclase, known to increase intracellular cAMP through the conversion of ATP into cAMP, thus affecting several intracellular pathways.
  • Lethal toxin is a zinc-dependent metaloproteinase known to interfere with the mitogen-activated protein kinase (MEK), thereby hampering multiple intracellular mechanisms.[1]

Cutaneous or Injection Anthrax

According to animal studies, spores that enter the skin of susceptible animals (either through a lesion or by injection) germinate and give rise, in about 2 - 4 hours, to a small edematous area containing capsulated bacilli. The following stages are noticed:[3]

Injection anthrax will have similar pathogenesis to cutaneous anthrax, but since it is injected, it can spread throughout the body faster and it becomes harder to recognize and treat than the cutaneous form.[9]

Inhalation Anthrax

In inhalation anthrax, the inhaled spores will be deposited in the alveoli first. From there, they will be transported, within phagocytic cells, through the lymphatic vessels to the mediastinal lymph nodes, where they will grow and cause hemorrhagic lymphadenitis. Bacteria escape from the damaged lymph nodes and invade the blood stream via the thoracic duct. Vegetative Bacillus then travel through the bloodstream and lymph vessels, potentially causing septicemia. At the same time toxins are released, causing tissue damage and hampering the immune system to facilitate bacterial spread.[10][11][12]

Once the bacteremia and associated toxemia reach a critical level, the severe symptoms that are characteristic of the acute phase of illness are manifested. During the acute phase, damage of the lung tissue becomes apparent on the X-ray. This damage results from the action of anthrax toxin on the endothelium of the lung’s capillary bed. Primary damage of the lung is not normally a feature of the initial phase of illness and primary pulmonary infection is an uncommon presentation.[13][11][12]

Studies in rhesus monkeys revealed that after spore inhalation, its germination might take up to 60 days. This is the reason why antibiotic prophylaxis is recommended for 60 days.[11]

Gastrointestinal Anthrax

In animal studies, the intestinal lesions caused by ingested anthrax spores range from focal to diffuse hemorrhagic necrotic enteritis of the small intestine. The tendency for localized lesions to develop in Peyer's patches suggests a possible role of the M cell in the uptake of the anthrax bacillus.[3]

Gross Pathology

Cutaneous and Injection Anthrax

Cutaneous infection typically produces ulcerated lesions which are covered by a scab and often contain numerous microorganisms. Anthrax eschars are generally seen on exposed unprotected regions of the body, mostly on the face, neck, hands and wrists. Generally cutaneous lesions are single, but sometimes two or more lesions are present.[14][15]

The lesions produced by injection anthrax will be similar to the ones of the cutaneous form. The difference will reside on the fact that injection anthrax can spread throughout the body faster and be harder to recognize and treat than cutaneous anthrax.[9]

Inhalational Anthrax

Gross pathologic lesions observed in non-human primates used in aerosol challenge models of inhalation anthrax include edema, congestion, hemorrhage, and necrosis in the lungs and mediastinum. Splenitis and necrotizing or hemorrhagic lymphadenitis involving the mediastinal, tracheobronchial, and other lymph nodes are common.[16] Primary pulmonary lesions, including those of pneumonia, are occasionally observed. Meningeal involvement ranging from edema, congestion, hemorrhage, and necrosis to suppurative or hemorrhagic meningitis, usually secondary to hematogenous spread from other types of anthrax, occurs in ≤77% of animals studied.[17] Autopsy findings from persons who died from inhalation anthrax in Sverdlovsk and in the United States[18] are consistent with findings from the non-human primates studies. Persons who died had extensive amounts of serosanguinous fluid in pleural cavities, edema, and hemorrhage of the mediastinum and surrounding soft tissues. 48% had cerebral edema, 21% had ascites, 17% had pericardial effusions, and 14% had petechial rash. Mediastinal lymph nodes and spleen also showed hemorrhage and necrosis.[16][19]

Gastrointestinal Anthrax

On gastrointestinal infection the typical eschar may occur on different locations, including:[11]

According to the location of the eschar, gastrointestinal anthrax may be divided in 2 categories: oropharyngeal and abdominal.[11]

As the eschar progresses, symptoms will appear as a result of the necrosis of the lesion, coupled with severe intestinal and mesenteric edema and lymph node enlargement in the mesentery.[11]

Microscopic Pathology

Anthrax lesions at any site are characterized by extensive necrosis and confluent exudate, containing macrophages and neutrophils. In histopathological specimens or culture media, the presence of large boxcar-shaped Gram-positive bacilli in chains suggests the diagnosis.

Cutaneous or Injection Anthrax

Histologic examination of skin lesions caused by cutaneous anthrax reveals:[20]

Inhalation Anthrax

Histologic evaluation of affected tissues reveals:

Gastrointestinal Anthrax

Histologic evaluation of affected tissues revealed:[20]

Gallery

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Liu, Shihui; Moayeri, Mahtab; Leppla, Stephen H. (2014). "Anthrax lethal and edema toxins in anthrax pathogenesis". Trends in Microbiology. 22 (6): 317–325. doi:10.1016/j.tim.2014.02.012. ISSN 0966-842X.
  2. 2.0 2.1 Hanna, Philip C.; Ireland, John A.W. (1999). "Understanding Bacillus anthracis pathogenesis". Trends in Microbiology. 7 (5): 180–182. doi:10.1016/S0966-842X(99)01507-3. ISSN 0966-842X.
  3. 3.0 3.1 3.2 3.3 "Anthrax in Humans and Animals" (PDF).
  4. Shadomy, Sean V.; Smith, Theresa L. (2008). "Anthrax". Journal of the American Veterinary Medical Association. 233 (1): 63–72. doi:10.2460/javma.233.1.63. ISSN 0003-1488.
  5. Ross, Joan M. (1957). "The pathogenesis of anthrax following the administration of spores by the respiratory route". The Journal of Pathology and Bacteriology. 73 (2): 485–494. doi:10.1002/path.1700730219. ISSN 0368-3494.
  6. Moayeri, M (2004). "The roles of anthrax toxin in pathogenesis". Current Opinion in Microbiology. 7 (1): 19–24. doi:10.1016/j.mib.2003.12.001. ISSN 1369-5274.
  7. Rubin, Raphael (2012). Rubin's pathology : clinicopathologic foundations of medicine. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 1605479683.
  8. Kumar, Vinay (2014). Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Elsevier/Saunders. ISBN 0323266169.
  9. 9.0 9.1 "Anthrax Symptoms".
  10. Turnbull, Peter (2008). Anthrax in humans and animals. Geneva, Switzerland: World Health Organization. ISBN 9789241547536.
  11. 11.0 11.1 11.2 11.3 11.4 11.5 Spencer RC (2003). "Bacillus anthracis". J Clin Pathol. 56 (3): 182–7. PMC 1769905. PMID 12610093.
  12. 12.0 12.1 Friedlander AM, Welkos SL, Pitt ML, Ezzell JW, Worsham PL, Rose KJ; et al. (1993). "Postexposure prophylaxis against experimental inhalation anthrax". J Infect Dis. 167 (5): 1239–43. PMID 8486963.
  13. Turnbull, Peter (2008). Anthrax in humans and animals. Geneva, Switzerland: World Health Organization. ISBN 9789241547536.
  14. Rubin, Raphael (2012). Rubin's pathology : clinicopathologic foundations of medicine. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 1605479683.
  15. Kumar, Vinay (2014). Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Elsevier/Saunders. ISBN 0323266169.
  16. 16.0 16.1 Guarner, Jeannette; Jernigan, John A.; Shieh, Wun-Ju; Tatti, Kathleen; Flannagan, Lisa M.; Stephens, David S.; Popovic, Tanja; Ashford, David A.; Perkins, Bradley A.; Zaki, Sherif R. (2003). "Pathology and Pathogenesis of Bioterrorism-Related Inhalational Anthrax". The American Journal of Pathology. 163 (2): 701–709. doi:10.1016/S0002-9440(10)63697-8. ISSN 0002-9440.
  17. Twenhafel, N. A. (2010). "Pathology of Inhalational Anthrax Animal Models". Veterinary Pathology. 47 (5): 819–830. doi:10.1177/0300985810378112. ISSN 0300-9858.
  18. A. A. Abramova & L. M. Grinberg (1993). "[Pathology of anthrax sepsis according to materials of the infectious outbreak in 1979 in Sverdlovsk (macroscopic changes)]". Arkhiv patologii. 55 (1): 12–17. PMID 7980032. Unknown parameter |month= ignored (help)
  19. A. A. Abramova & L. M. Grinberg (1993). "[Pathology of anthrax sepsis according to materials of the infectious outbreak in 1979 in Sverdlovsk (macroscopic changes)]". Arkhiv patologii. 55 (1): 12–17. PMID 7980032. Unknown parameter |month= ignored (help)
  20. 20.0 20.1 Dixon, Terry C.; Meselson, Matthew; Guillemin, Jeanne; Hanna, Philip C. (1999). "Anthrax". New England Journal of Medicine. 341 (11): 815–826. doi:10.1056/NEJM199909093411107. ISSN 0028-4793.
  21. 21.000 21.001 21.002 21.003 21.004 21.005 21.006 21.007 21.008 21.009 21.010 21.011 21.012 21.013 21.014 21.015 21.016 21.017 21.018 21.019 21.020 21.021 21.022 21.023 21.024 21.025 21.026 21.027 21.028 21.029 21.030 21.031 21.032 21.033 21.034 21.035 21.036 21.037 21.038 21.039 21.040 21.041 21.042 21.043 21.044 21.045 21.046 21.047 21.048 21.049 21.050 21.051 21.052 21.053 21.054 21.055 21.056 21.057 21.058 21.059 21.060 21.061 21.062 21.063 21.064 21.065 21.066 21.067 21.068 21.069 21.070 21.071 21.072 21.073 21.074 21.075 21.076 21.077 21.078 21.079 21.080 21.081 21.082 21.083 21.084 21.085 21.086 21.087 21.088 21.089 21.090 21.091 21.092 21.093 21.094 21.095 21.096 21.097 21.098 21.099 21.100 21.101 21.102 21.103 21.104 21.105 21.106 21.107 21.108 21.109 21.110 21.111 21.112 21.113 21.114 "Public Health Image Library (PHIL), Centers for Disease Control and Prevention".

Template:WikiDoc Sources